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Diss Factsheets

Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
not stated
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report date:
1993

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1992-07-17
Deviations:
yes
Remarks:
Positive control was missing.
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 1993-09-23
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The conduct of this study was prior to the establishment of the LLNA method (OECD 429).

Test material

Constituent 1
Chemical structure
Reference substance name:
1-[({[(1R,2S,5R)-5-methyl-2-(propan-2-yl)cyclohexyl]oxy}carbonyl)oxy]propan-2-ol
EC Number:
607-858-0
Cas Number:
260781-16-6
Molecular formula:
C14H26O4
IUPAC Name:
1-[({[(1R,2S,5R)-5-methyl-2-(propan-2-yl)cyclohexyl]oxy}carbonyl)oxy]propan-2-ol

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 290 to 309 g
- Housing: opaque PPL (Type IV) cages, two or three to a cage; bedding: softwood sawdust "Hahnflock H 3/4"
- Diet (ad libitum): pelleted diet, "3113 Altromin"
- Water (ad libitum): vitamin C enriched tap water acidified to pH 2.5 with HCI
- Acclimation period: four days

ENVIRONMENTAL CONDITIONS
- Temperature: 21 ± 3°C,
- Relative humidity: 55 ± 15%.
- Air changes: 10 times/hour
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
other: Oleum arachidis Ph. Eur. 2nd
Concentration / amount:
5 % w/w of the test item
Day(s)/duration:
day 1
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100 % of the test item
Day(s)/duration:
day 8 (duration: 48 hours)
Adequacy of induction:
non-irritant substance, but skin pre-treated with 10% SDS
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100 % of the test item
Day(s)/duration:
Day 22 (duration: 24 hours)
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
10 guinea pigs
Details on study design:
RANGE FINDING TESTS:
On the basis of the preliminary investigations the doses for the main study were chosen.
The intradermal irritancy of the test article was investigated in order to find the minimal irritant test article concentration for the intradermal induction using intradermal injections as in the main study. The following test item concentrations were tested: 0.63 %, 1.25 %, 2.5 %, and 5 % in oleum arachidis.

The topical irritancy of the test article was investigated in order to find the minimal irritant test article concentration for the dermal induction and the maximum non-irritating test article concentration for the challenge application using procedures similar to the main study. The following test item concentrations were tested: 25 %, 50 %, and 100 %.

Results:
intradermal injection: a very discrete erythema was observed following intradermal injection of the four concentrations.
topical application: no erythema was observed following closed patch application, neither on the back nor on the flanks.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal injection and dermal application)
- Site: area of dorsal skin 4 x 6 cm in the scapular region was clipped free of pair with an electric clipper.
- Frequency of applications: three pairs of intradermal injections were given once and 6 days later the same site was treated with approximately 0.5 g sodium lauryl sulphate (10% in petrolatum) to provoke a mild inflammatory reaction. 24 hours later 0.4 mL of the test item was topically applied to the skin using a patch.
- Exposure period: 48 hours (dermal application)
- Concentrations:
Test animals:
Intradermal:
i) 0.1 mL FCA diluted 1:1 with sterile distilled water
ii) 0.1 mL test article in oleum arachidis (final concentration: 5 % (w/w))
iii) 0.1 mL test article and FCA in the ratio 1:1 (final concentration: 10 % (w/w))
Topical application:
100 % test material

Control animals:
Intradermal injection:
i) 0.1 mL FCA diluted 1:1 with sterile distilled water
ii) 0.1 mL oleum arachidis
iii) 0.1 mL oleum arachidis and FCA in the ratio 1:1 (w/w)
Topical application:
oleum arachidis

B. CHALLENGE EXPOSURE
- No. of exposures: 1 (topical application three weeks after the intradermal induction)
- Exposure period: 24 hours
- Site: flanks (right flank: oleum arachidis; left flank: 100 % of the test item)
- Evaluation (hr after challenge): 24 and 48 hours after removal of the patch
Evaluation according to the Magnusson and Kligman grading scale.
Challenge controls:
5 guinea pigs were used as control animals
Challenge dose: 100 % of the test item
Positive control substance(s):
no

Results and discussion

Positive control results:
no data

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100 % of test item
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No positive skin responses were observed. The guinea pigs made normal body weight increases over the duration of the study and exhibited normal appearance and behaviour.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100 % of test item
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No positive skin responses were observed. The guinea pigs made normal body weight increases over the duration of the study and exhibited normal appearance and behaviour.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100 % of test item
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
No positive skin responses were observed. The guinea pigs made normal body weight increases over the duration of the study and exhibited normal appearance and behaviour.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100 % of test item
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
No positive skin responses were observed. The guinea pigs made normal body weight increases over the duration of the study and exhibited normal appearance and behaviour.

Any other information on results incl. tables

Induction

Intradermal injections of Freund's complete adjuvant mixed with test article extract or vehicle elicited skin irritation. No skin reactions were observed following the intradermal and dermal induction with the extracts.

The intradermal injections gave a discrete erythema using 5 % test article in Oleum arachidis. No skin reactions were observed following dermal induction using 100 % test article.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The substance is not a skin sensitiser.
According to Regulation (EC) No 1272/2008 and subsequent adaptations, the substance does not require classification as skin sensitiser.
Executive summary:

The skin sensitisation potential of the substance was investigated according to the guinea pig maximization test (OECD guideline 406 (1992)) using 10 Dunkin-Hartley guinea pigs. A control group of 5 animals were run concurrently.

The treatment regime involved an intradermal induction (5 % of the substance in oleum arachidis Ph. Eur. 2nd) and a topical induction (100 % of the substance; occlusive dressing, exposure period: 48 hours). The day before topical induction the skin was treated with 10% sodium lauryl sulfate in petrolatum. The control animals were treated with oleum arachidis during the intradermal induction and the topical induction.

Both control and test animals were subjected to a topical challenge exposure (test item concentration: 100 % of the substance, occlusive dressing, exposure period: 24 hours) three weeks after the intradermal induction. Administration sites were examined for erythema and oedema formation at 24 and 48 hours after removal of the test item application and scored according to the Magnusson and Kligman grading scale.

The sensitisation rate of the test item was 0 % at 24 hours and at 48 hours after patch removal.The test item is not considered to be a skin sensitiser.

According to the EC-Regulation 1272/2008 and subsequent regulations, the test substance is not classified as skin sensitiser.